We are continuing linkage studies in an effort to identify the location of genes which predispose individuals to stuttering. To accomplish our initial linkage scan, we plan to enroll 400 affected relative pairs. Over the past year, we made contact with 175 new potential families. From these contacts, we have enrolled 140 new individuals, bringing our total enrollment to 130 affected pairs. Together with other members of these families, we have built our DNA sample collection to 275 individuals. We have also begun the clinical evaluation of all subjects, to confirm and refine our diagnoses. So far we have completed evaluations on 95 subjects, and we expect to have evaluations on an additional 150 subjects completed by the end of October, 1998. We have been obtaining our DNA samples via buccal swab rather than from blood. Use of our buccal swab procedure greatly lowers barriers to participation and allows us to enroll many individuals who would otherwise refuse. However, the amounts of DNA obtained are much lower than those obtained from blood. Therefore, we have developed reliable methods of whole-genome amplification, along with robust genotyping methods for this amplified DNA. We have initiated pilot genotyping studies to help plan the large-scale genotyping that will be undertaken. To help identify and enroll additional families, we have made contact with a number of stuttering therapy programs. Our first such collaboration has been with the Hollins Communications Research Institute, in Roanoke, VA. We are presently in discussions with other large programs, and hope to establish other collaborations. Other linkage studies in human communication We have initiated a number of linkage studies in other areas of human communication. With Dr. Christy Ludlow, we have been obtaining blood samples and purifying genomic DNA from families with a number of voice and speech disorders that are known or suspected to be inherited, including cluttering, vocal fold paralysis, and spastic dysphonia. Over the past year we have accumulated DNA samples from a total of 42 individuals in 9 different families. We plan to initiate genotyping studies in these families when the number of individuals reaches sufficient size. We have also become involved in the Utah Genetic Reference Project (UGRP) in an attempt to identify the loci of the genes underlying the two most common specific chemosensory deficits in Caucasians, the ability to taste phenylthiocarbamide (PTC) and the ability to smell adrostenone. The UGRP is a re-evaluation of the so-called CEPH families, which have been used for generalized linkage studies and construction of the normal human linkage maps. Since large numbers of genotypes exist for these family members, knowledge of their phenotypes will allow linkage studies to be performed without additional laboratory genotyping. In the past year, 9 families have been evaluated for PTC tasting and 8 for the ability to smell androstenone. A number of families appear to segregate each of these traits, suggesting we will be able to identify linkages for the genetic loci which underlie these deficits.